In the past Genomics has faced a lot of controversy, particularly in relation to eugenics. Even today, applications of genomics, such as genetic engineering provoke a lot of ethical and societal debate. Nevertheless, during these dark times, it is important to reflect upon how genomics has positively impacted society and the hopes for its application in the future. In this blog, we provide examples of the broad impact genomics has had on society, from crime intervention to vaccine development.
Crime and exoneration
One of the major benefits of genetic technology has been its application in law enforcement. In 2018, according to the FBI, 400,000 cases used DNA evidence to aid in criminal investigations. The use of genetic genealogy databases became prominent in California when law enforcement officers were investigating the Golden State Killer. The team uploaded the genetic profile of a sample of DNA from the crime scene to a genetic genealogy database. From this, they were able to reconstruct a large family tree, which eventually led them to their suspect. Nevertheless, access of law enforcement to these genealogy databases, such as 23andMe, has caused concern. As a result, careful consideration of the ethical, legal and safeguarding issues is vital. Most use of genetic genealogy by law enforcement currently occurs in the US.
On the other hand, genetic technology within criminology has been used to exonerate innocent individuals. The Innocence Project is a non-profit legal organisation that is committed to exonerating individuals who were wrongly convicted. The project uses DNA testing to reform the criminal justice system and prevent future injustices. It was founded in 1992 by Barry Scheck and Peter Neufeld, who formed the so-called ‘dream team’ of lawyers that defended O.J. Simpson in his murder trial.
As of January 2020, the Innocence Project has documented over 365 DNA exonerations in the United States. Of these cases, 21 were previously sentenced to death. These exonerees spent an average of 14 years in prison. The overwhelmingly majority of these crimes had black defendants and white victims (80%). One such case involves Darryl Hunt who was exonerated after serving 19 years in prison of a life sentence for the rape and murder of newspaper copy editor, Deborah Sykes.
Despite initial public concerns, genetically modified organisms (GMOs) have become an important component of modern agriculture. Genetic engineering has allowed for precise control over the genetic changes introduced into an organism. Within agriculture, GMOs have allowed for increased crop yields, reduced costs for food production, reduced need for pesticides, enhanced nutrient composition and food quality, and resistance to pests and disease. Importantly, GMOs provide food security and medical benefits for a growing population.
In 1994, a GMO tomato was the first GMO produce created through genetic engineering. It became available for sale after studies proved it was as safe as traditionally bred tomatoes. Since then, other GMO products created through genetic engineering have become available to consumers, including corn and soybeans. Interestingly, 95% of animals used for meat and dairy in the United States eat GMO crops. Several independent studies have reported no difference in how GMO and non-GMO foods affect the health and safety of animals.
Other experimental examples include Enviro-Pig. Through genetic engineering, this pig emits 30-60% less phosphorous than traditional pigs. As a result, this aims to lessen livestock impact on the environment.
GMOs are heavily regulated by government agencies. Most regulations require mandatory labelling of GMOs sold to consumers.
With the completion of the Human Genome Project and subsequent technological advancements, efforts in medicine have shifted from the ‘one size fits all’ approach to more tailored therapies based on a patient’s information (largely genetic). The aim of precision medicine is to improve patient treatment and care. Currently, the two most promising areas of precision medicine have been seen within rare diseases and oncology.
There are over 7,000 rare diseases. For many patients with rare diseases, there is a long ‘diagnostic odyssey’ to identify the cause of their condition. There have been monumental efforts in diagnosing patients with rare conditions, with aims to offer whole-genome sequencing as part of routine care. NHS Wales took the first steps in this goal, by launching a new genetic service – WINGS. This is the first diagnostic service to use high-throughput technology to test critically ill babies and children with unexplained rare disorders.
Other progress can be seen within the UK’s 100,000 Genomes Project, which sequenced the genomes of patients with rare diseases and cancer. One of the first results from this study impacted a four-year old child named Jessica. The study found that Jessica had a mutation in the SLC2A1 gene which resulted in Glut1 deficiency syndrome (Jessica’s diagnosis). Fortunately, this syndrome can be treated with a ‘ketogenic diet’ that can help reduce the number of seizures patients experience.
A hallmark of cancer is genomic instability. Cancer continuously evolves due to selective pressures, resulting in enormous heterogeneity within and across individuals. Tailoring of cancer treatment is essential to improve patient response and prevent relapse due to resistance.
Genomic technologies are globally used to prevent and diagnose cancers. The most common test is BRCA1/2 predictive testing. Patients at high-risk, if eligible, can undergo genetic testing to determine whether they have inherited BRCA1/2 mutations. This process allows patients to manage the risk of developing cancer and in some cases, reduces stress and anxiety that comes from not knowing.
However, genomic technology is continually evolving, providing more in depth understanding of different cancers. This has become apparent in the development of targeted therapeutics. For example, chronic myeloid leukaemia is often driven by the gene rearrangement BCR-ABL. This aberration can be targeted using tyrosine kinase inhibitors, such as imatinib, which prevent the BCR-ABL enzyme from functioning.
More recently, interest has shifted towards analysing nucleic components within the blood to help diagnose and detect relapses within cancer patients. Liquid biopsy in several studies has been shown to offer accurate, rapid genotyping for adoption into routine clinical care.
Drugs and Vaccines
Genomics can also aid in drug and vaccine development, providing insight into potential candidates and patient stratification.
Candidate selection and development
Aside from oncology, genomics has provided important insight into drug discovery and vaccine development processes. In many cases, vaccine and therapeutic development has shifted from microbiological to sequence-based approaches. Multi-omic approaches have also improved the process of identifying targets and predicting their effects in patients.
With ongoing emergence of infectious diseases, vaccines and therapies have become an essential component of controlling the spread of disease. Genome sequencing of various infectious diseases has revealed the genetic repertoire of antigens and drug targets from which novel candidates can be identified. It is estimated that 10-100 times more candidates can be found in 1-2 years using genomic-based approaches than can be identified using conventional methods.
Genome sequencing has the ability to identify genetic patterns related to the virulence of a disease as well as what genetic factors contribute to immunity or successful vaccine response. For example, the HPV vaccine is a vaccine containing viral proteins manufactured in yeast cells using recombinant DNA technology.
Elsewhere, our knowledge of all human genes and their functions has changed drug research and discovery processes. Genomic sequencing provides a large amount of data that can offer valuable insight into the identification of novel drug targets. Furthermore, individual variation presents additional opportunities for drug discovery. Genomics has also been important within drug development processes. For example, the first synthetic human insulin was produced in 1978 using Escherichia coli. Biosynthetic human insulin has since become commercially available, with the vast majority of insulin used worldwide being biosynthetic.
In the last decade, attention has been drawn to exploring the role of the genome in drug response. Specifically, it analyses how genetic variation can impact individual response to drugs. The aim of pharmacogenomics is to optimise drug therapy and minimise adverse effects. A key example of pharmacogenomics can be seen within warfarin dosing. VKORC1 and CYP2C9 are key enzymes that interact with warfarin. Variations within these genes can impact warfarin dosage. They are useful for identifying the risk of bleeding during warfarin administration.
The benefits of genomics can be seen across society, from freeing the innocent to tackling infectious diseases. A running theme of all these applications is the benefit to human life. Our ability to sequence and understand genomes, as well as manipulate them, has enabled us to have a profoundly positive impact on society. As technologies advance, ethical, social and legal questions will arise that need to once again put the benefit to human life at the forefront.
I for one hope that sooner rather than later, I can come back to this post and insert a section describing genomics’ contribution to the eradication of COVID-19.
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